1. Field of the Invention
This invention relates to the field of flow regulation in fluidic devices. Specifically, this invention relates to the field of flow regulation in fluidic devices used in the field of chemical synthesis and analysis.
2. Background of the Invention
Many different methods have been developed for sample preparation, chemical synthesis and chemical analysis. Typical methods include continuous flow analysis and discrete batch analysis. Continuous flow analysis includes establishing a sample pipeline to enable high sample throughput independent of the complexity of the reaction. For instance, continuous flow analysis includes the ability to perform in-line sample treatments such as distillation, digestion, dialysis and solvent extraction in addition to performing complex reactions requiring the sequential addition of multiple reagents. Continuous flow sample processing enables a pipeline to be established which requires a defined amount of time for a reaction followed by processing of one sample within a defined cycle period which is significantly shorter than the reaction time for complex reactions. The major drawbacks to continuous flow analysis include the lack of ability to program tests per sample and excessive reagent usage as they are pumped continuously during the analytical process.
Beyond the analytical difficulties with current methods, continuous flow instruments are negatively impacted by the use of peristaltic pumps to provide motive force for samples and reagents. These pumps limit the performance of continuous flow systems through the peristaltic action that is an intrinsic characteristic of peristaltic pumps. This action causes pulsations in the fluid path that may adversely affect the accurate quantification of analytes passing through the fluidic device to a sample detector. Although they are relatively inexpensive, peristaltic pumps can be problematic for common applications involving sample measurements. For example, the tubing for each of the analytical streams or channels must frequently be replaced, which requires a subsequent clean-up process. Sizing issues must also be rectified in order to achieve proper quantitative “mixing” of analyte and reagents both spatially and volumetrically. Peristaltic pumps typically have a limited number of analytical channels, which each have a limited relative volume. Furthermore, the tubing used in peristaltic pumps often fails due to collapse (i.e., loss of elasticity). This tubing failure generates uneven, or non-reproducible flows, for the different channels of analyte and/or reagents being transported.
Other pumps are also not particularly suitable for a variety of reasons. For example, replacing peristaltic pumps with syringe pumps is very expensive. Moreover, other types of air displacement pumps are not suitable replacements for peristaltic pumps, because they have problems with gas solubility (e.g., air bubbles coming out of solution in the detector) and gas compressibility in the analyte transport process.
Discrete batch analysis operates by adding only the exact amount of reagents required per test per sample, which allows for automated test selection per sample and significant reduction in reagent usage. For instance, discrete batch analysis includes minimizing sample volumes, reagent volumes, and waste generation as well as providing a higher level of automation than continuous flow analysis in test profiling per sample and automated method switching. However, discrete batch analysis has major drawbacks that include (a) decreased sample throughput or number of tests per hour since each sample reaction sequence is treated discretely or independently thereby not enabling a pipeline to be established; and (b) the inability to perform in-line sample preparation.